3,3-dialkoxy-2-hydroxyiminopropionitriles, process for preparation thereof and process of preparing 5-amino-4-nitrosopyrazoles or salts thereof by the use of the same

ABSTRACT

The present invention is to provide a 3,3-dialkoxy-2-hydroxyiminopropionitrile represented by the formula (1): 
     
       
         
         
             
             
         
       
         
         
           
             wherein R 1  and R 2  may be the same or different from each other, and each represent an alkyl group having 1 to 8 carbon atoms,
 
a process for preparing the same, and a process for preparing a 5-amino-4-nitrosopyrazole compound represented by the formula (4):
 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             wherein R 4  represents a hydrogen atom, an alkyl group which may have a substituent(s) or an aryl group which may have a substituent(s),
 
or an acid salt thereof using the same.

This application is the United States national phase application ofInternational Application PCT/JP02/05827 filed Jun. 12, 2002.

1. Technical Field

The present invention relates to a novel3,3-dialkoxy-2-hydroxyiminopropionitrile which is useful as anintermediate starting material for medicines, agricultural chemicals andothers, and a process for producing the same, and further relates to aprocess for producing a 5-amino-4-nitrosopyrazole compound or an acidsalt which is useful as an intermediate starting material for medicines,agricultural chemicals and others using the same.

2. Background Art

The 3,3-dialkoxy-2-hydroxyiminopropionitrile of the present invention isa novel compound and a process for producing the same has neverconventionally been known.

On the other hand, 5-amino-4-nitrosopyrazole compound can be utilized asa synthetic starting material of 4,5-diaminopyrazole compound, etc.,which is useful as a hair dye or an intermediate for an antitumor agent(for example, Japanese Provisional Patent Publication No. Sho. 60-56981(which corresponds to DE 3432983), Japanese Provisional PatentPublication No. Sho. 62-273979, and Japanese PCT Provisional PatentPublication No. Hei. 7-502542 (which corresponds to U.S. Pat. No.5,663,366)).

In the prior art, as a preparation method of 5-amino-4-nitrosopyrazolecompound or an acid salt thereof, for example, in Japanese ProvisionalPatent Publication No. Sho. 62-273979, there is disclosed a method ofobtaining 5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole hydrochloride byreacting isoamyl nitrite with 5-amino-1-(2-hydroxyethyl)-pyrazole in thepresence of hydrogen chloride. However, according to this method, thereare problems that the pyrazole used as a starting material cannot easilybe obtained and a yield of the objective material is low.

An object of the present invention is to provide a novel3,3-dialkoxy-2-hydroxyiminopropionitrile and a process for producing thesame.

Another object of the present invention is to provide a process forproducing a 5-amino-4-nitrosopyrazole compound or an acid salt thereofin a high yield by a simple and easy method from starting materialseasily available.

SUMMARY OF THE INVENTION

The present invention relates to a3,3-dialkoxy-2-hydroxyiminopropionitrile represented by the followingformula (1):

-   -   wherein R¹ and R² may be the same or different from each other,        and represent an alkyl group having 1 to 8 carbon atoms.

The present invention also relates to a process for producing the3,3-dialkoxy-2-hydroxyiminopropionitrile represented by theabove-mentioned formula (1) which comprises reacting a3-alkoxyacrylonitrile represented by the following formula (2):

-   -   wherein R³ represents an alkyl group having 1 to 4 carbon atoms,        with a nitrosyl halide in the presence of an alcohol.

The present invention further relates to a 5-amino-4-nitrosopyrazolecompound represented by the following formula (4):

-   -   wherein R⁴ represents a hydrogen atom, an alkyl group which may        have a substituent(s) or an aryl group which may have a        substituent(s),        or an acid salt thereof,        which comprises reacting the        3,3-dialkoxy-2-hydroxyimino-propionitrile represented by the        above-mentioned formula (1) with a hydrazine compound        represented by the formula (3):        H₂NNHR⁴ (3)

wherein R⁴ has the same meaning as defined above, in the presence of anacid.

The present invention further relates to a process for producing the5-amino-4-nitrosopyrazole compound represented by the above-mentionedformula (4) which comprises reacting the 3-alkoxyacrylonitrilerepresented by the above-mentioned formula (2) with a nitrosyl halide inthe presence of an alcohol, and then, further reacting the hydrazinecompound represented by the above-mentioned formula (3) in the presenceof an acid.

BEST MODE FOR CARRYING OUT THE INVENTION

The 3,3-dialkoxy-2-hydroxyiminopropionitrile according to the presentinvention is shown by the above-mentioned formula (1).

In the formula (1), R¹ and R² may be the same or different from eachother, and represent an alkyl group having 1 to 8 carbon atoms,specifically, there may be mentioned, for example, a methyl group, anethyl group, a propyl group, a butyl group, a pentyl group, a hexylgroup, a heptyl group and an octyl group, preferably a methyl group anda butyl group. These groups may include the respective isomers.Incidentally, 3,3-dialkoxy-2-hydroxyiminopropionitrile of the presentinvention has an oxime group, so that some isomers exist such as Eisomer, Z isomer and the like, and any isomers are included in thepresent invention.

Incidentally, the above-mentioned3,3-dialkoxy-2-hydroxyiminopropionitrile can be led to a5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole hydrochloride representedby the following formula (5):

by reacting it with a 2-hydroxyethylhydrazine in the presence ofhydrochloric acid (mentioned in Example 4 below), and the5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole hydrochloride thus led canbe utilized as a synthetic starting material for a pyrazolopyrazinecompound which is an effective ingredient of an antitumor agent asmentioned above (for example, Japanese Provisional Patent PublicationsNo. 60-56981, No. 62-273979, and Japanese PCT Provisional PatentPublication No. 7-502542).

The 3,3-dialkoxy-2-hydroxyiminopropionitrile of the present inventioncan be obtained by reacting the 3-alkoxy-acrylonitrile represented bythe above-mentioned formula (2) with a nitrosyl halide in the presenceof an alcohol.

In the formula (2), R³ represents an alkyl group having 1 to 4 carbonatoms, and, for example, it is a methyl group, an ethyl group, a propylgroup or a butyl group. These groups may also include various kinds ofisomers.

As an alcohol to be used in the reaction of the present invention, theremay be mentioned an alcohol having an alkyl group having 1 to 8 carbonatoms (including various kinds of isomers), and there may be used, forexample, methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butylalcohol, t-butyl alcohol, pentyl alcohol, hexyl alcohol, heptyl alcoholand octyl alcohol, preferably methanol, ethanol, n-propyl alcohol,isopropyl alcohol, n-butyl alcohol, t-butyl alcohol, more preferablymethanol.

An amount of the above-mentioned alcohol is preferably 0.5 to 100 mols,more preferably 0.8 to 50 mols based on 1 mol of the3-alkoxyacrylonitrile.

Incidentally, the alcohol may be directly added to the reaction system,but an alcohol which is simultaneously formed at the time of generatingnitrosyl halide in the system as mentioned below may be utilized.

As the nitrosyl halide to be used in the reaction of the presentinvention, there may be mentioned nitrosyl fluoride, nitrosyl chloride,nitrosyl bromide and nitrosyl iodide, and nitrosyl chloride ispreferably used.

As the above-mentioned nitrosyl halide, commercially available productsmay be used as such, but, a nitrosyl halide may be formed and used by,for example, (1) a method in which an alkyl nitrite and a hydrogenhalide are reacted (a nitrosyl halide and an alkyl alcohol are formed),or (2) a method in which an alkali metal nitrite and a hydrogen halideare reacted (a nitrosyl halide and an alkali metal halogenated salt areformed) and the like.

Incidentally, as a supplying method of the nitrosyl halide to thereaction system, commercially available products or the separatelygenerated nitrosyl halide by the above-mentioned method (1) or (2) maybe supplied, and the reaction of the above-mentioned method (1) or (2)may be directly carried out in the reaction system and the generatednitrosyl halide may be used (at that case, alkyl alcohol (in the case of(1)) or an alkali metal halogenated salt (in the case of (2)) isgenerated in the reaction system.). Also, the nitrosyl halide may bediluted with a gas inactive to the reaction.

An amount of the above-mentioned nitrosyl halide to be used ispreferably 0.5 to 10 mols, more preferably 0.8 to 5 mols based on 1 molof the 3-alkoxyacrylonitrile.

The reaction of the present invention is carried out in the presence orabsence of a solvent. When the solvent is used, it is not specificallylimited so long as it does not inhibit the reaction, and there may bementioned, for example, alcohols such as methanol, ethanol, n-propylalcohol, isopropyl alcohol, n-butyl alcohol, t-butyl alcohol, etc.;nitrites such as acetonitrile, propionitrile, etc.; ethers such asdiethyl ether, tetrahydrofuran, dioxane, etc.; halogenated aliphatichydrocarbons such as methylene chloride, chloroform, carbontetrachloride, etc.; aromatic hydrocarbons such as benzene, toluene,etc.; halogenated aromatic hydrocarbons such as chlorobenzene, etc.;carboxylic acids such as acetic acid, propionic acid, etc., and analcohol is preferably used.

An amount of the above-mentioned solvent to be used is optionallyadjusted depending on uniformity or stirrability of the reactionmixture, and it is preferably 0 to 100 g, more preferably 0 to 50 gbased on 1 g of the alkoxyacrylonitrile.

The reaction of the present invention can be carried out by a method inwhich, for example, the 3-alkoxyacrylonitrile and an alcohol are mixedand a nitrosyl halide is supplied thereto to effect the reaction, andthe like. A reaction temperature at that time is preferably −70 to 50°C., more preferably −30 to 40° C., and a reaction pressure is notparticularly limited.

The 3,3-dialkoxy-2-hydroxyiminopropionitrile obtained by the reaction ofthe present invention can be isolated and purified after completion ofthe reaction by a general means such as crystallization,recrystallization, distillation, column chromatography and the like.

Incidentally, in the present invention, the resulting3,3-dialkoxy-2-hydroxyiminopropionitrile is reacted with the hydrazinecompound represented by the formula (3) without isolation to produce the5-amino-4-nitrosopyrazole compound represented by the formula (4).

The hydrazine compound to be used in the reaction of the presentinvention is represented by the above-mentioned formula (3). In theformula (3), R⁴ represents a hydrogen atom, an alkyl group which mayhave a substituent(s) or an aryl group which may have a substituent(s).As the above-mentioned alkyl group, there may be mentioned, for example,a methyl group, an ethyl group, a propyl group, a butyl group, a pentylgroup, a hexyl group and a heptyl group, etc., and as theabove-mentioned aryl group, there may be mentioned, for example, aphenyl group, a naphthyl group, a pyridyl group, a pyrimidyl group, apyrazyl group, a pyridazyl group, a quinolyl group, etc. Incidentally,these groups may include various kinds of isomers. Also, as theabove-mentioned substituent(s), there may be mentioned, for example, ahydroxyl group; an alkyl group such as a methyl group, an ethyl group, apropyl group, a butyl group, etc. (these groups may include variouskinds of isomers.); an alkoxy group such as a methoxy group, an ethoxygroup, a propoxy group, a butoxy group, etc. (these groups may includevarious kinds of isomers.); an aryl group such as a phenyl group, athienyl group, a furyl group, a pyridyl group, a pyrimidyl group, etc.;a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom,an iodine atom, etc.; and a nitro group. Incidentally, the position or anumber of the substituent(s) is not specifically limited. In the presentinvention, as the preferred alkyl group or aryl group of R⁴, there maybe mentioned, for example, a methyl group, an ethyl group, a propylgroup, an isopropyl group, a n-butyl group, a t-butyl group, a phenylgroup, etc., as the preferred substituted alkyl group or aryl group,there may be mentioned, for example, a 2-hydroxyethyl group, a2-hydroxypropyl group, a benzyl group, a 2-chlorobenzyl group, a4-chlorobenzyl group, a 4-methylphenyl group, a 4-methoxyphenyl group, a2-chlorophenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group, a2,6-dichloro-4-trifluoromethylphenyl group, a3-chloro-5-trifluoromethylpyridin-2-yl group, etc., as the furtherpreferred alkyl group or aryl group, there may be mentioned, forexample, a methyl group, an ethyl group, a t-butyl group, a phenylgroup, etc., and as the further preferred substituted alkyl group oraryl group, there may be mentioned, for example, a 2-hydroxyethyl group,a benzyl group, a 4-methylphenyl group, a 4-methoxyphenyl group, a4-chlorophenyl group, etc.

An amount of the above-mentioned hydrazine compound to be used ispreferably 0.5 to 2.0 mol, more preferably 0.7 to 1.5 mol based on 1 molof the 3,3-dialkoxy-2-hydroxyiminopropionitrile.

As the acid to be used in the reaction of the present invention, theremay be mentioned, for example, a mineral acid such as hydrochloric acid,sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid,hydroiodic acid, etc.; an organic carboxylic acid such as acetic acid,propionic acid, etc.; and an organic sulfonic acid such asmethanesulfonic acid, benzenesulfonic acid, etc., preferably a mineralacid, more preferably hydrochloric acid or sulfuric acid is used.Incidentally, these acids may be used singly or in admixture of two ormore kinds. In the present invention, an acid salt of the5-amino-4-nitrosopyrazole compound corresponding to the acid to be usedcan be obtained.

An amount of the above-mentioned acid to be used is preferably 0.1 to 20mol, more preferably 0.8 to 5 mol based on 1 mol of3,3-dialkoxy-2-hydroxyiminopropionitrile.

The reaction of the present invention is carried out in the presence orabsence of a solvent. When the solvent is used, it is not specificallylimited so long as it does not inhibit the reaction, and there may bementioned, for example, water; an alcohol such as methanol, ethanol,n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, t-butyl alcohol,etc.; an ether such as diethyl ether, tetrahydrofuran, dioxane, etc.; anamide such as N,N-dimethylformamide, etc.; a sulfoxide such asdimethylsulfoxide, etc.; an aliphatic hydrocarbon such as pentane,hexane, heptane, cyclohexane, etc.; an aromatic hydrocarbon such asbenzene, toluene, xylene, etc.; a halogenated hydrocarbon such asmethylene chloride, chloroform, 1,2-dichloroethane, etc.; a nitrile suchas acetonitrile, propionitrile, etc.; a carboxylic acid such as aceticacid, propionic acid, etc.; an ester such as ethyl acetate, butylacetate, ethyl propionate, etc., preferably water; an alcohol, morepreferably water; methanol, ethanol and/or isopropyl alcohol is used.Incidentally, these solvents may be used alone or in admixture of two ormore kinds.

An amount of the above-mentioned solvent to be used may be optionallycontrolled depending on the uniformity or stirrability of the reactionsolution, and it is preferably 0 to 100 g, more preferably 0 to 50 g,particularly preferably 0 to 30 g based on 1 g of3,3-dialkoxy-2-hydroxyiminopropionitrile.

The reaction of the present invention can be carried out, for example,by mixing an acid, 3,3-dialkoxy-2-hydroxyiminopropionitrile, a hydrazinecompound and a solvent, and stirring the mixture, etc. The reactiontemperature at that time is preferably −20 to 150° C., more preferably 0to 90° C., and a reaction pressure is not specifically limited.

The reaction in the other embodiment of the present invention is carriedout, for example, by mixing 3,3-dialkoxy-2-hydroxyiminopropionitrile andan alcohol, supplying a nitrosyl halide, reacting preferably at −70 to70° C., more preferably −30 to 40° C. under stirring, then, adding anacid, a hydrazine compound and a solvent to the mixture, and reactingthem preferably at −20 to 150° C., more preferably 0 to 90° C. understirring, etc. A reaction pressure at that time is not specificallylimited.

An acid salt of the 5-amino-4-nitrosopyrazole compound can be obtainedby the reaction of the present invention, and the resulting compound isneutralized by a base (for example, aqueous ammonia) to obtain a5-amino-4-nitrosopyrazole compound in a free form. Incidentally,5-amino-4-nitrosopyrazole compound or an acid salt thereof can beisolated and/or purified by an usual method such as crystallization,recrystallization, condensation, column chromatography, etc.

EXAMPLE

Next, the present invention will be explained specifically by referringto Examples, but the scope of the present invention is not limited bythese Examples.

Example 1 Synthesis of 3,3-dimethoxy-2-hydroxyiminopropionitrile

To a flask having an inner volume of 300 ml and equipped with a stirringdevice, a thermometer, a condenser and a gas inlet tube were charged42.83 g (0.5 mol) of 3-methoxyacrylonitrile with a purity of 97% byweight and 125 ml of methanol, and the mixture was cooled to −10° C.under stirring. Then, the reaction solution was maintained to −10 to 0°C., and while feeding nitrosyl chloride generated by reacting 170.5 g(1.0 mol) of 41% by weight aqueous sodium nitrite solution and 320 ml(3.5 mol) of conc. hydrochloric acid (the above-mentioned method (2)) ina separate apparatus to the reaction solution, the resulting mixture wasreacted at −10 to 0° C. for 3 hours and at room temperature for 2 hours.After completion of the reaction, the reaction mixture was concentratedunder reduced pressure, the concentrate was washed in the order ofn-hexane and toluene, dried under reduced pressure at 40° C. to obtain61.6 g of 3,3-dimethoxy-2-hydroxyiminopropionitrile (Isolation yield:80.1%) as a pale yellowish solid with a purity of 93.7% by weight(absolute calibration curve method by high performance liquidchromatography).

The 3,3-dimethoxy-2-hydroxyiminopropionitrile is a novel compound havingthe following physical properties.

Melting point; 113 to 116° C. EI-MS (m/z); 113, 75, 54 CI-MS (m/z); 145(MH⁺)

¹H-NMR (CDCl₃, δ (ppm)); 3.46 (6H, s), 4.97 (1H, s), 8.82 (1H, brs) IR(KBr method, cm⁻¹); 3242, 3215, 2234, 1450, 1038, 933, 798 Elementalanalysis; Carbon: 41.40%, Hydrogen: 5.53%, Nitrogen: 19.44%

(Theoretical value (C₅H₈N₂O₃); Carbon: 41.67%, Hydrogen: 5.59%,Nitrogen: 19.44%)

Example 2 Syntheses of 3,3-di-n-butoxy-2-hydroxyiminopropionitrile,3-n-butoxy-2-hydroxyimino-3-methoxypropionitrile and3,3-dimethoxy-2-hydroxyiminopropionitrile

At room temperature, 5.0 g (60 mmol) of 3-methoxyacrylonitrile, 6.5 g(60 mmol) of n-butyl nitrite and 30 ml of diethyl ether were mixed.Then, 5 ml of the above-mentioned solution was added to a flask havingan inner volume of 25 ml and equipped with a stirring device. Understirring, 1 ml (6 mmol) of a 25.7% by weight hydrogen chloride methanolsolution was gradually added dropwise, to generate nitrosyl halide andn-butyl alcohol in the reaction system (the method of theabove-mentioned (1)), and the mixture was reacted at room temperaturefor one hour. After completion of the reaction, the reaction mixture wasconcentrated under reduced pressure, and after adding water to theconcentrate, the mixture was extracted with toluene. The organic layerwas taken out, washed with a saturated aqueous sodium hydrogen carbonatesolution, and dried over anhydrous magnesium sulfate. After filtration,the filtrate was concentrated under reduced pressure, the concentratewas purified by silica gel column chromatography (Filler; Wako gel C-200(available from Wako Junyaku Co.), Eluent; toluene/ethyl acetate=10/1(volume ratio)) to obtain 0.06 g (Isolation yield: 4%) of3,3-di-n-butoxy-2-hydroxyiminopropionitrile as colorless oily product,0.21 g (Isolation yield: 19%) of3-n-butoxy-2-hydroxyimino-3-methoxypropionitrile as colorless oilyproduct and 0.14 g of 3,3-dimethoxy-2-hydroxyiminopropionitrile(Isolation yield: 16%) as white solid.

The 3,3-di-n-butoxy-2-hydroxyiminopropionitrile and3-n-butoxy-2-hydroxyimino-3-methoxypropionitrile are novel compoundshaving the following physical properties.

Physical Properties of 3,3-di-n-butoxy-2-hydroxyiminopropionitrile

CI-MS (m/z); 229 (MH⁺), 200, 155, 126 ¹H-NMR (CDCl₃, δ (ppm)); 0.93 (6H,t), 1.34 to 1.66 (8H, m), 3.50 to 3.71 (4H, m), 6.47 (1H, s), 8.55 (1H,s)

Physical Properties of 3-n-butoxy-2-hydroxyimino-3-methoxypropionitrile

CI-MS (m/z); 187 (MH⁺), 155, 113, 84 ¹H-NMR (CDCl₃, δ ppm)); 0.94 (3H,t), 1.35 to 1.68 (4H, m), 3.46 (3H, s), 3.51 to 3.72 (2H, m), 5.02 (1H,s), 9.14 (1H, s)

Example 3 Synthesis of 3,3-dimethoxy-2-hydroxyiminopropionitrile

To a flask having an inner volume of 100 ml and equipped with a stirringdevice and a dropping funnel were charged 3.0 g (36 mmol) of3-methoxyacrylonitrile, 9.0 g (63 mmol) of a 25.7% by weight hydrogenchloride methanol solution and 15 ml of methanol. Under stirring, 4.7 g(43 mmol) of n-butyl nitrite was gradually added dropwise to the mixtureto generate nitrosyl halide and n-butyl alcohol in the system (themethod of the above-mentioned (1)), and the mixture was reacted at roomtemperature for 26 hours. After completion of the reaction, a saturatedsodium hydrogen carbonate was added to the mixture to neutralize themixture, and methanol was removed from the reaction mixture bydistillation under reduced pressure. The aqueous layer was extractedwith ethyl acetate, the organic layer was taken out, washed with asaturated saline solution, and dried over anhydrous magnesium sulfate.After filtration, the filtrate was concentrated under reduced pressure,the concentrate was recrystallized from toluene to obtain 2.6 g of3,3-dimethoxy-2-hydroxyiminopropionitrile (Isolation yield: 50%) aswhite solid.

Example 4 Synthesis of 5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazoleHydrochloride

To a flask having an inner volume of 100 ml and equipped with a stirringdevice, a thermometer and a reflux condenser were charged 8.43 g (55mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile with a purity of94.0% by weight synthesized in the same manner as in Example 1, 4.01 g(50 mmol) of 2-hydroxyethylhydrazine with a purity of 95% by weight, 50ml of ethanol and 7.60 g (75 mmol) of conc. hydrochloric acid, and themixture was reacted under reflux (76 to 79° C.) for one hour. Aftercompletion of the reaction, the reaction mixture was concentrated underreduced pressure, 20 ml of toluene and 20 ml of isopropyl alcohol wereadded to the concentrate, and the mixture was stirred at roomtemperature for one hour. Then, the solution was filtered and thefiltrate was dried at 40° C. under reduced pressure to obtain 6.85 g of5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole hydrochloride (Isolationyield: 67.4%) as yellow solid with a purity of 94.8% by weight (absolutecalibration curve method by high performance liquid chromatography).

Incidentally, physical properties of the5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole hydrochloride are asmentioned below.

Melting point; 164.8 to 166.6° C. (decomposed) ¹H-NMR(DMSO-d₆, δ (ppm));3.65 to 4.13 (4H, m), 6.80 to 10.40 (5H, m) IR (KBr method, cm¹); 3290,3063, 2635, 1670, 1623, 1208, 1099, 1063, 1002, 716

Example 5 Synthesis of 5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazoleHydrochloride

To a flask having an inner volume of 25 ml and equipped with a stirringdevice, a thermometer and a reflux condenser were charged 1.47 g (10.0mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile with a purity of98.1% by weight synthesized in the same manner as in Example 1, 0.84 g(10.5 mmol) of 2-hydroxyethylhydrazine with a purity of 95% by weight,10 ml of methanol and 1.5 ml (18.0 mmol) of conc. hydrochloric acid, andthe mixture was reacted under reflux (67° C.) for 1.5 hours. Aftercompletion of the reaction, when the reaction mixture was analyzed byhigh performance liquid chromatography (absolute calibration curvemethod), it was found that 1.81 g of5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole hydrochloride (Reactionyield: 93.8%) had been formed.

Example 6 Synthesis of 5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazolehydrogensulfate

To a flask having an inner volume of 25 ml and equipped with a stirringdevice, a thermometer and a reflux condenser were charged 1.47 g (10.0mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile with a purity of98.1% by weight synthesized in the same manner as in Example 1, 0.84 g(10.5 mmol) of 2-hydroxyethylhydrazine with a purity of 95% by weight,0.54 ml of water, 10 ml of methanol and 1.18 g (12.0 mmol) of conc.sulfuric acid, and the mixture was reacted under reflux (66 to 67° C.)for 3 hours. After completion of the reaction, when the reaction mixturewas analyzed by high performance liquid chromatography (absolutecalibration curve method), it was found that 2.24 g of5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole hydrogen sulfate (Reactionyield: 88.2%) had been formed.

Example 7 Synthesis of 5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazoleHydrochloride

To a flask having an inner volume of 200 ml and equipped with a stirringdevice, a thermometer and a reflux condenser were charged 16.86 g (110mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile with a purity of94.0% by weight synthesized in the same manner as in Example. 1, 8.02 g(100 mmol) of 2-hydroxyethylhydrazine with a purity of 95% by weight,100 ml of ethanol and 10 ml (120 mmol) of conc. hydrochloric acid, andthe mixture was reacted under reflux (76 to 77° C.) for one hour. Aftercompletion of the reaction, when the reaction mixture was analyzed byhigh performance liquid chromatography (absolute calibration curvemethod), it was found that 17.62 g of5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole hydrochloride (Reactionyield: 91.5%) had been formed.

Example 8 Synthesis of 5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazoleHydrochloride

To a flask having an inner volume of 25 ml and equipped with a stirringdevice, a thermometer and a reflux condenser were charged 3.37 g (22mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile with a purity of94.0% by weight synthesized in the same manner as in Example 1, 1.60 g(20 mmol) of 2-hydroxyethylhydrazine with a purity of 95% by weight, 9.6ml of isopropyl alcohol and 2 ml (24 mmol) of conc. hydrochloric acid,and the mixture was reacted under reflux (79 to 80° C.) for one hour.After completion of the reaction, when the reaction mixture was analyzedby high performance liquid chromatography (absolute calibration curvemethod), it was found that 3.35 g of5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole hydrochloride (Reactionyield: 86.9%) had been formed.

Example 9 Synthesis of 5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole

To a flask having an inner volume of 25 ml and equipped with a stirringdevice and a thermometer were charged 2.10 g (10 mmol) of5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole hydrochloride with a purityof 91.6% by weight synthesized in the same manner as in Example 4, 3.5ml of water and 0.5 ml of isopropyl alcohol. Then, 1 ml (16 mmol) of 28%aqueous ammonia was gradually added dropwise to the mixture, and theresulting mixture was reacted for 30 minutes while maintaining theliquid temperature to 5° C. or lower. After completion of the reaction,precipitated crystals were collected by filtration. Then, the crystalswere washed with 1 ml of cold water and 1 ml of cold isopropyl alcohol,and then dried at 40° C. under reduced pressure to obtain 1.13 g of5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole (Isolation yield: 72.0%) asreddish orange crystal with a purity of 99.7% by weight (absolutecalibration curve method by high performance liquid chromatography).

Incidentally, physical properties of the5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole are as mentioned below.

Melting point; 170.2 to 171.8° C. (decomposed) ¹H-NMR (DMSO-d₆, δ(ppm)); 3.60 to 4.03 (4H, m), 4.75 to 5.03 (1H, br), 7.06 (0.2H, s),7.76 to 8.29 (2H, br), 8.53 (0.8H, s) IR (KBr method, cm⁻¹); 3346, 3168,2960, 1658, 1529, 1497, 1243, 1072, 1016, 913, 624

Example 10 Synthesis of 5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole

To a flask having an inner volume of 50 ml and equipped with a stirringdevice, a thermometer and a reflux condenser were charged 4.59 g (30mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile with a purity of94.3% by weight synthesized in the same manner as in Example 1, 2.98 g(31.5 mmol) of 2-hydroxyethylhydrazine with a purity of 80.5% by weight,7.8 ml of methanol and 4.5 ml (54 mmol) of conc. hydrochloric acid, andthe mixture was reacted at 50 to 52° C. for 3 hours. After completion ofthe reaction, 7 ml of water was added to the mixture and the resultingmixture was cooled up to 10° C. Then, 3.5 ml (58 mmol) of 28% by weightaqueous ammonia was gradually added dropwise to the mixture, and themixture was stirred for 30 minutes while maintaining the liquidtemperature to 5° C. or lower. The precipitated crystals were collectedby filtration, and then, the crystals were washed with 2.5 ml of coldwater and 2.5 ml of cold methanol, and dried under reduced pressure toobtain 3.40 g of 5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole (Isolationyield: 69.7%) as reddish orange crystals with a purity of 96.0% byweight (absolute calibration curve method by high performance liquidchromatography).

Example 11 Synthesis of 5-amino-1-methyl-4-nitrosopyrazole

To a flask having an inner volume of 25 ml and equipped with a stirringdevice, a thermometer and a reflux condenser were charged 2.97 g (20mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile with a purity of96.9% by weight, 1.01 g (21 mmol) of methylhydrazine with a purity of97% by weight, 6 ml of methanol and 3.0 ml (36 mmol) of conc.hydrochloric acid, and the mixture was reacted at 50 to 52° C. for 4hours. After completion of the reaction, 5 ml of water was added to themixture to cool the mixture up to 10° C., and 2.3 ml (37.9 mmol) of 28%by weight aqueous ammonia was gradually added dropwise to the mixture,and the resulting mixture was stirred for 30 minutes while maintainingthe liquid temperature to 5° C. or lower. Precipitated crystals werecollected by filtration, and then, the crystals were washed with 1.2 mlof cold water and 1.2 ml of cold methanol, and dried under reducedpressure to obtain 1.91 g of 5-amino-1-methyl-4-nitrosopyrazole(Isolation yield: 74.8%) as dark purple solid with a purity of 98.8% byweight (absolute calibration curve method by high performance liquidchromatography).

Incidentally, physical properties of the5-amino-1-methyl-4-nitrosopyrazole are as mentioned below.

¹H-NMR (DMSO-d₆, δ (ppm)); 3.51 (2.4H, s), 3.58 (0.6H, s), 7.02 (0.2H,s), 7.85 to 8.20 (2H, br), 8.51 (0.8H, s) IR (KBr method, cm⁻¹); 3369,3173, 1648, 1524, 1424, 1296, 1187, 1007, 937, 830, 562

Example 12 Synthesis of 5-amino-1-t-butyl-4-nitrosopyrazole

To a flask having an inner volume of 25 ml and equipped with a stirringdevice, a thermometer and a reflux condenser were charged, 2.97 g (20mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile with a purity of96.9% by weight synthesized in the same manner as in Example 1, 2.70 g(21 mmol) of t-butylhydrazine hydrochloride with a purity of 97% byweight, 1.4 ml of water, 6 ml of methanol and 1.3 ml (15 mmol) of conc.hydrochloric acid, and the mixture was reacted at 60 to 62° C. for 3hours. After completion of the reaction, 5 ml of water was added to themixture and the mixture was cooled up to 10° C. Then, 2.3 ml (37.9 mmol)of 28% by weight aqueous ammonia was gradually added dropwise to themixture, and the resulting mixture was stirred for 30 minutes whilemaintaining the liquid temperature to 5° C. or lower. Precipitatedcrystals were collected by filtration, and then, the crystals werewashed with 1.2 ml of cold water and 1.2 ml of cold methanol, and driedunder reduced pressure to obtain 1.93 g of5-amino-1-t-butyl-4-nitrosopyrazole (Isolation yield: 55.2%) as reddishorange solid with a purity of 96.2% by weight (absolute calibrationcurve method by high performance liquid chromatography).

Incidentally, physical properties of the5-amino-1-t-butyl-4-nitrosopyrazole are as mentioned below.

¹H-NMR (DMSO-d₆, δ (ppm)); 1.53 (7.2H, s), 1.58 (1.8H, s), 6.99 (0.2H,s), 7.80 to 8.30 (2H, br), 8.48 (0.8H, s) IR (KBr method, cm⁻¹); 3345,3160, 2983, 1632, 1524, 1478, 1238, 1079, 835, 607

Example 13 Synthesis of 5-amino-1-benzyl-4-nitrosopyrazole

To a flask having an inner volume of 25 ml and equipped with a stirringdevice, a thermometer and a reflux condenser were charged, 2.97 g (20mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile with a purity of96.9% by weight synthesized in the same manner as in Example 1, 3.43 g(21 mmol) of benzylhydrazine hydrochloride with a purity of 97% byweight, 1.4 ml of water, 6 ml of methanol and 1.3 ml (15 mmol) of conc.hydrochloric acid, and the mixture was reacted at 50 to 52° C. for 3hours. After completion of the reaction, 5 ml of water was added to themixture to cool the mixture up to 10° C. Then, 2.3 ml (37.9 mmol) of 28%by weight aqueous ammonia was gradually added dropwise to the mixture,and the resulting mixture was stirred for 30 minutes while maintainingthe liquid temperature to 5° C. or lower. Precipitated crystals werecollected by filtration, and then, the crystals were washed with 5 ml ofcold water and dried under reduced pressure to obtain 3.89 g of5-amino-1-benzyl-4-nitrosopyrazole (Isolation yield: 82.8%) as brownsolid with a purity of 86.1% by weight (absolute calibration curvemethod by high performance liquid chromatography).

Incidentally, physical properties of the5-amino-1-benzyl-4-nitrosopyrazole are as mentioned below.

¹H-NMR (DMSO-d₆, δ (ppm)); 5.16 (1.5H, s), 5.23 (0.5H, s), 7.04 to 7.53(5.25H, m), 8.15 to 8.50 (2H, br), 8.59 (0.75H, s) IR (KBr method,cm⁻¹); 3354, 3160, 3033, 1647, 1523, 1488, 1453, 1254, 1219, 1055, 957,836, 699

Example 14 Synthesis of 5-amino-4-nitroso-1-phenylpyrazole

To a flask having an inner volume of 25 ml and equipped with a stirringdevice, a thermometer and a reflux condenser were charged, 2.97 g (20mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile with a purity of96.9% by weight synthesized in the same manner as in Example 1, 2.32 g(21 mmol) of phenylhydrazine with a purity of 98% by weight, 10 ml ofmethanol and 3.0 ml (36 mmol) of conc. hydrochloric acid, and themixture was reacted at 50 to 52° C. for one hour. After completion ofthe reaction, 10 ml of water was added to the mixture to cool the sameup to 10° C., then, 2.3 ml (37.9 mmol) of 28% by weight aqueous ammoniawas gradually added dropwise to the mixture, and the resulting mixturewas stirred for 30 minutes while maintaining the liquid temperature to5° C. or lower for 30 minutes. Precipitated crystals were collected byfiltration, and the crystals were washed with 5 ml of cold water anddried under reduced pressure to obtain 3.19 g of5-amino-4-nitroso-1-phenylpyrazole (Isolation yield: 63.4%) as anocherous solid with a purity of 74.9% by weight (absolute calibrationcurve method by high performance liquid chromatography).

Incidentally, physical properties of the5-amino-4-nitroso-1-phenylpyrazole are as mentioned below.

¹H-NMR (DMSO-d₆, δ (ppm)); 6.83 to 7.31 (5H, m), 7.69 (0.5H, d), 8.00(0.5H, d), 11.00 (0.5H, s), 11.29 (0.5H, s), 12.80 to 13.75 (1H, br) IR(KBr method, cm⁻¹); 3279, 2255, 1605, 1559, 1495, 1262, 1170, 1002, 876,754, 689, 621, 504

Example 15 Synthesis of 5-amino-1-(4-methylphenyl)-4-nitrosopyrazole

To a flask having an inner volume of 25 ml and equipped with a stirringdevice, a thermometer and a reflux condenser were charged, 2.97 g (20mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile with a purity of96.9% by weight synthesized in the same manner as in Example 1, 3.40 g(21 mmol) of 4-methylphenylhydrazine hydrochloride with a purity of 98%by weight, 1.4 ml of water, 10 ml of methanol and 1.3 ml (15 mmol) ofconc. hydrochloric acid, and the mixture was reacted at 50 to 52° C. forone hour. After completion of the reaction, 15 ml of water and 5 ml ofmethanol were added to the mixture to cool the same up to 10° C., and2.3 ml (37.9 mmol) of 28% by weight aqueous ammonia was gradually addeddropwise to the mixture, and the resulting mixture was stirred for 30minutes while maintaining the liquid temperature to 5° C. or lower.Precipitated crystals were collected by filtration, and then, thecrystals were washed with 15 ml of cold water and dried under reducedpressure to obtain 3.26 g of5-amino-1-(4-methylphenyl)-4-nitrosopyrazole (Isolation yield: 67.3%) asa yellowish solid with a purity of 83.5% by weight (absolute calibrationcurve method by high performance liquid chromatography).

Incidentally, physical properties of the5-amino-1-(4-methylphenyl)-4-nitrosopyrazole are as mentioned below.

¹H-NMR (DMSO-d₆, δ (ppm)); 2.22 (1.35H, s), 2.24 (1.65H, s), 6.93 to7.13 (4H, m), 7.66 (0.45H, s), 7.96 (0.55H, d), 10.91 (0.45H, s), 11.22(0.55H, s), 12.70 to 13.70 (1H, br) IR (KBr method, cm⁻¹); 3281, 3255,2258, 1616, 1550, 1507, 1258, 1177, 1025, 872, 811, 506

Example 16 Synthesis of 5-amino-1-(4-chlorophenyl)-4-nitrosopyrazole

To a flask having an inner volume of 25 ml and equipped with a stirringdevice, a thermometer and a reflux condenser were charged 2.97 g (20mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile with a purity of96.9% by weight synthesized in the same manner as in Example 1, 3.96 g(21 mmol) of 4-chlorophenylhydrazine hydrochloride with a purity of 95%by weight, 1.4 ml of water, 10 ml of methanol and 1.3 ml (15 mmol) ofconc. hydrochloric acid, and the mixture was reacted at 50 to 52° C. for2 hours. After completion of the reaction, 25 ml of water and 5 ml ofmethanol were added to the mixture to cool the same up to 10° C., and2.3 ml (37.9 mmol) of 28% by weight aqueous ammonia was gradually addeddropwise to the mixture and the resulting mixture was stirred for 30minutes while maintaining the liquid temperature to 5° C. or lower.Precipitated crystals were collected by filtration, and then, thecrystals were washed with 10 ml of cold water and dried under reducedpressure to obtain 3.73 g of5-amino-1-(4-chlorophenyl)-4-nitrosopyrazole (Isolation yield: 74.3%) asa yellowish solid with a purity of 88.7% by weight (absolute calibrationcurve method by high performance liquid chromatography).

Incidentally, physical properties of the5-amino-1-(4-chlorophenyl)-4-nitrosopyrazole are as mentioned below.

¹H-NMR (DMSO-d₆, δ (ppm)); 7.02 to 7.38 (4H, m), 7.70 (0.45H, s), 8.01(0.55H, s), 11.10 (0.45H, s), 11.38 (0.55H, s), 12.90 to 13.80 (1H, br)IR (KBr method, cm⁻¹); 3267, 2254, 1604, 1550, 1489, 1255, 1171, 1090,1007, 875, 825, 507

Example 17 Synthesis of 5-amino-1-(4-methoxyphenyl)-4-nitrosopyrazole

To a flask having an inner volume of 25 ml and equipped with a stirringdevice, a thermometer and a reflux condenser were charged, 2.97 g (20mmol) of 3,3-dimethoxy-2-hydroxyiminopropionitrile with a purity of96.9% by weight synthesized in the same manner as in Example 1, 3.74 g(21 mmol) of 4-methoxyphenylhydrazine hydrochloride with a purity of 98%by weight, 1.4 ml of water, 10 ml of methanol and 1.3 ml (15 mmol) ofconc. hydrochloric acid, and the mixture was reacted at 50 to 52° C. forone hour. After completion of the reaction, 25 ml of water and 5 ml ofmethanol were added to the mixture to cool the same up to 10° C., and2.3 ml (37.9 mmol) of 28% by weight aqueous ammonia was gradually addeddropwise to the mixture and the resulting mixture was stirred for 30minutes while maintaining the liquid temperature to 5° C. or lower.Precipitated crystals were collected by filtration, and then, thecrystals were washed with 10 ml of cold water and dried under reducedpressure to obtain 3.07 g of5-amino-1-(4-methoxyphenyl)-4-nitrosopyrazole (Isolation yield: 55.3%)as a yellowish solid with a purity of 78.6% by weight (absolutecalibration curve method by high performance liquid chromatography).

Incidentally, physical properties of5-amino-1-(4-methoxyphenyl)-4-nitrosopyrazole are as mentioned below.

¹H-NMR (DMSO-d₆, δ (ppm)); 3.70 (1.35H, s), 3.71 (1.65H, s), 6.86 to7.07 (4H, m), 7.63 (0.45H, d), 7.93 (0.55H, d), 10.87 (0.45H, s), 11.19(0.55H, s), 12.70 to 13.50 (1H, br) IR (KBr method, cm⁻¹); 3305, 3013,2264, 1552, 1515, 1465, 1227, 1174, 1008, 832, 571, 525

Example 18 Synthesis of 5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole

To a flask having an inner volume of 500 ml and equipped with a stirringdevice, a thermometer, a reflux condenser and a gas inlet tube werecharged 42.5 g (0.50 mol) of 97.7% by weight 3-methoxyacrylonitrile and165 ml of methanol, and the mixture was cooled up to 15° C. understirring. Then, while maintaining the reaction solution to 15 to 25° C.,nitrosyl chloride generated by reacting 171.1 g (1.0 mol) of 41% byweight aqueous sodium nitrite solution and 304.2 g (3.0 mol) of 36% byweight hydrochloric acid in a separate vessel was fed to the reactionsolution over 1.5 hours, and the mixture was reacted at 15 to 20° C. forone hour under stirring.

Then, nitrogen was blown in the reaction solution to remove nitrosylchloride, a mixed solution of 42.3 g (0.5 mol) of 80.5% by weight2-hydroxyethylhydrazine and 60.8 g (0.60 mol) 36% by weight hydrochloricacid was gradually added to the reaction solution while maintaining thetemperature thereof to 50° C., and the mixture was reacted at 50° C. for3 hours under stirring. After completion of the reaction, 120 ml ofwater was added to the reaction mixture to make the liquid temperature10° C., and 70 ml (1.12 mol) of 28% by weight aqueous ammonia wasgradually added to the mixture to neutralize the same, so that crystalswere precipitated. Moreover, the reaction mixture was cooled up to 5° C.and stirred for 30 minutes. Crystals were collected by filtration,washed successively with 30 ml of cold water and 30 ml of cold methanoland dried under reduced pressure to obtain 57.5 g of5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole (Isolation yield: 69.8%) asred-orange crystals with a purity of 94.8% by weight (absolutecalibration curve method by high performance liquid chromatography).

Example 19 Synthesis of 5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole)

To a flask having an inner volume of 100 ml and equipped with a stirringdevice, a thermometer, a gas inlet tube and a dry ice condenser (ethanoland dry ice were charged in a Dewar condenser) were charged, 10.28 g(0.12 mol) of 97.0% by weight 3-methoxyacrylonitrile and 30 ml ofmethanol, and the mixture was cooled up to 5° C. while stirring. Then,while maintaining the temperature of the reaction solution to 5 to 20°C., nitrosyl chloride generated by reacting 34.0 g (0.20 mol) of 41% byweight aqueous sodium nitrite solution and 60.8 g (0.60 mol) of 36% byweight hydrochloric acid in a separate vessel were fed to the reactionvessel over 40 minutes, and the mixture was reacted for 2 hours understirring at 5 to 20° C.

Then, an inner atmosphere of the reaction vessel was replaced withnitrogen, and 7 ml of methanol and nitrosyl halide were removed underreduced pressure. To the reaction solution were gradually added 13 ml ofmethanol, 9.61 g (0.12 mol) of 95% by weight 2-hydroxyethylhydrazine and14.6 g (0.14 mol) of 36% by weight hydrochloric acid in this order, andthe mixture was reacted for 3 hours under stirring at 50° C. Aftercompletion of the reaction, 30 ml of water was added to the reactionmixture to cool the same to 10° C., and 15 ml (0.25 mol) of 28% byweight aqueous ammonia was gradually added to neutralize the mixture, sothat crystals were precipitated. Moreover, the reaction mixture wascooled up to 5° C. and stirred for 30 minutes. Crystals were collectedby filtration, washed successively with 8 ml of cold water and 8 ml ofcold methanol and dried under reduced pressure to obtain 13.46 g of5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole (Isolation yield: 70.1%) asred-orange crystals with a purity of 97.6% by weight (absolutecalibration curve method by high performance liquid chromatography).

Example 20 Synthesis of 5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole

To a flask having an inner volume of 500 ml and equipped with a stirringdevice, a thermometer, a reflux condenser and a gas inlet tube werecharged 50.0 g (0.59 mol) of 97.0% by weight 3-methoxyacrylonitrile and177 ml of methanol, and the mixture was cooled to 15° C. under stirring.Then, while maintaining the temperature of the reaction solution to 15to 25° C., nitrosyl chloride generated by reacting 203.4 g (1.18 mol) of41% by weight aqueous sodium nitrite solution and 359.0 g (3.54 mol) of36% by weight hydrochloric acid in a separate vessel were fed to thereaction solution over 1.5 hours, and the mixture was reacted for onehour under stirring at 15 to 20° C.

Then, nitrogen was blown into the reaction solution to remove nitrosylchloride, and 18 ml of methanol was added thereto to cool the same up to10° C. To the reaction solution was gradually added 56.1 g (0.59 mol) of80.0% by weight 2-hydroxyethylhydrazine, and 71.8 g (0.60 mol) of 36% byweight hydrochloric acid was gradually added to the same whilemaintaining the solution to 50° C., and the mixture was reacted understirring at the same temperature for 3 hours. After completion of thereaction, 150 ml of water was added to the reaction mixture to make theliquid temperature 10° C., and 87 ml (1.43 mol) of 28% by weight aqueousammonia was gradually added to the mixture to neutralize the same, sothat crystals were precipitated. Moreover, the reaction mixture washeated to 40° C. and stirred for 20 minutes, then, cooled up to 5° C.and stirred for 30 minutes. Crystals were collected by filtration,washed with 70 ml of cold water and dried under reduced pressure toobtain 63.0 g of 5-amino-1-(2-hydroxyethyl)-4-nitrosopyrazole (Isolationyield: 67.4%) as red-orange crystals with a purity of 98.6% by weight(absolute calibration curve method by high performance liquidchromatography).

UTILIZABILITY IN INDUSTRY

According to the present invention, a novel3,3-dialkoxy-2-hydroxyiminopropionitrile which is useful as anintermediate starting material for medicine, agricultural chemical,etc., and a process for preparing the same can be provided.

Also, according to the present invention, it can be provided a processfor preparing an objective 5-amino-4-nitrosopyrazole compound or an acidsalt thereof with a high yield from the above-mentioned3,3-dialkoxy-2-hydroxyiminopropionitrile which can be easily availablewith a simple and easy method.

1. A 3,3-dialkoxy-2-hydroxyiminopropionitrile represented by the formula(1):

wherein R¹ and R² may be the same or different from each other, and eachrepresent an alkyl group having 1 to 8 carbon atoms.
 2. The3,3-dialkoxy-2-hydroxyiminopropionitrile according to claim 1, whereinR¹ and R² may be the same or different from each other, and eachrepresent a methyl group or a butyl group.
 3. A process for preparing a3,3-dialkoxy-2-hydroxyiminopropionitrile represented by the formula (1):

wherein R^(‘)and R² may be the same or different from each other, andeach represent an alkyl group having 1 to 8 carbon atoms, whichcomprises reacting a 3-alkoxyacrylonitrile represented by the formula(2):

wherein R³ represents an alkyl group having 1 to 4 carbon atoms, with anatrosyl halide in the presence of an alcohol.
 4. The process accordingto claim 3, wherein the alcohol as an alcohol having an alkyl group with1 to 8 carbon atoms.
 5. The process according to claim 3, wherein thealcohol is at least one selected from the group consisting of methanol,ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, t-butylalcohol, pentyl alcohol, hexyl alcohol, heptyl alcohol and octylalcohol.
 6. The process according to claim 3, wherein the alcohol is atleast one selected from the group consisting of methanol, ethanol,n-propyl alcohol, isopropyl alcohol, n-butyl alcohol and t-butylalcohol.
 7. The process according to claim 3, wherein the alcohol isused in an amount of 0.5 to 100 mol per mol of the3-alkoxyacrylonitrile.
 8. The process according to claim 3, wherein thealcohol is used in an amount of 0.8 to 50 mol per mol of the3-alkoxyacrylonitrile.
 9. The process according to claim 3, wherein thenitrosyl halide is used in an amount of 0.5 to 10 mol per mol of the3-alkoxyacrylonitrile.
 10. The process according to claim 3, wherein thenitrosyl halide is used in an amount of 0.8 to 5 mol per mol of the3-alkoxyacrylonitrile.